Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To investigate clinical features and risk factors of childhood diabetes mellitus(DM)complicated with urinary tract infection(UTI).Methods The data of 160 children with DM in our hospital in the past 2 years were collected as the research object,and they were divided into the UTI group and the non-UTI group UTI,with 80 cases in each group.The clinical data of children with DM and UTI were collected and analyzed,including DM type,sex,age,body mass index(BMI),living environment,duration of disease,length of hospital stay,indwelling catheter,ketoacidosis,antibiotic and insulin use,the types of bacteria isolated from urine samples and various laboratory indicators on admission.Results Pathogen bacteria mainly included Escherichia coli(n=37,46.2%),Enterococci(n=21,26.2%)and Klebsiella pneumoniae(n=9,11.2%)in the UTI group.Univariate analysis showed that there were significant differences in obesity,duration of disease,length of hospital stay,indwelling catheter,ketoacidosis,antibiotic use,glycosylated hemoglobin(HbA1c),albumin(ALB)and serum creatinine(Cr)between the two groups(P＜0.05).Multivariate regression analysis showed that risk factors for DM complicating UTI included prolonged hospitalization(OR=2.087,95%CI:1.562-2.789),indwelling urinary catheter(OR=15.886,95%CI:2.336-108.007),ketoacidosis(OR=9.300,95%CI:1.169-73.992),duration of disease≥36 months(OR=20.548,95%CI:2.425-174.119),increased HbA1c(OR=16.686,95%CI:3.666-75.955)and serum Cr(OR=1.010,95%CI:1.002-1.019),while the increased serum ALB(OR=0.799,95%CI:0.702-0.910)was its protective factor.Conclusion Pathogenic bacteria in the UTI group are mainly Escherichia coli.Children with DM and UTI are closely related to the length of hospitalization,indwelling catheter,ketoacidosis,duration of disease,HbA1c,serum Cr and ALB levels.

Objective:To investigate whether interleukin(IL)-1β is involved in pyroptosis which leads to mouse islet β cell line βTC-6 cell damage, and to explore the role of JNK inhibitor SP600125 in inhibiting IL-1β induced βTC-6 cell pyroptosis.Methods:βTC-6 cell line and mouse islets were incubated with IL-1β for 48 h or intervened with both JNK inhibitor SP600125 and IL-1R antagonist IL-1Ra, then GSDMD expression and β cell pyroptosis morphology were detected by immunofluorescence staining of GSDMD and DAPI. The expression levels of Gsdmd, IL-1β and IL-18 mRNAs were detected by real time fluorescence PCR, and apoptosis was examined by Annexin-V/7-AAD staining combined with flow cytometry.Results:βTC-6 cell pyroptotic body was significantly increased in the IL-1β treated group compared with the control group, and the expressions of pyroptosis related genes Gsdmd, IL-1β, and IL-18 mRNA were significantly higher( P<0.05), and apoptosis was increased, suggesting that IL-1β effectively induced the βTC-6 cell pyroptosis, IL-1Ra prevented IL-1β induced βTC-6 cell pyroptosis. In the presence of JNK inhibitor SP600125, IL-1β treatment failed to induce the expressions of Gsdmd and IL-18 mRNA, markers of pyroptosis, and reduced the rate of apoptosis, indicating that SP600125 suppressed IL-1β induced βTC-6 cell pyroptosis. Conclusion:Pyroptosis is one of the mechanisms of βTC-6 cell impairment caused by IL-1β, and SP600125, a JNK inhibitor, can block the IL-1β induced pyroptosis pathway and has a potential role in inhibiting βTC-6 cell pyroptosis.

Nonketotic hyperglycinemia(NKH), also known as glycine encephalopathy, is a rare and life-threatening autosomal recessive disease.Due to the insufficient activity of the glycine cleavage enzyme system(GCS), glycine can not be degraded and accumulates in the body.It leads to progressive damage to the nervous system.The clinical manifestations of the disease vary.Based on ultimate outcome, NKH is categorized into severe NKH and attenuated NKH.It is characterized by increased glycine level in cerebrospinal, and further confirmatory tests are molecular genetic testing and enzymatic testing.So far, no causal treatment of NKH has been discovered and the overall prognosis is still poor.The therapy is based on sodium benzoate and N-methyl-D-aspartate(NMDA)receptor site antagonists.This article reviews the progress of NKH, in order to help clinicians comprehensively identify NKH and take proactive measures to get the best results.

21-hydroxylase deficiency(21-OHD) is mainly characterized by cortisol deficiency with or without aldosterone deficiency and hyperandrogenemia.The disease requires lifelong exogenous glucocorticoid/salt supplementation.Excessive doses of exogenous glucocorticoids are often needed to control hyperandrogenemia, but the effect is not satisfactory.Corticotropin releasing factor (CRF) type 1 receptor antagonist can directly block the production of adrenocorticotropin, inhibit the generation of adrenogenic androgen, reduce the dose of glucocorticoid therapy, and thus lower the incidence of adverse reactions.In this article, the current research progress on 21-OHD therapy and CRF1 receptor antagonist was reviewed.

The hypothalamic-pituitary-thyroid axis gradually becomes mature at gestational age of 30~35 weeks.With the improvement of the treatment level of premature infants, the gestational age of surviving premature infants gradually decreases, and the thyroid axis of young premature infants is immature.Meanwhile, premature infants are more prone to systemic complications, such as ischemia and hypoxia, severe infection, etc., which aggravate the influence on thyroid.Clinically, more and more premature infants are found to be complicated with congenital hypothyroidism, temporary hypothyroxemia, hyperthyrotropin, delayed thyrotropin elevation, low T 3 syndrome and other problems.Abnormal thyroid function affects the outcome of the treatment of premature infant diseases.Early detection and early treatment is the key to improve the treatment, metabolism and the development of premature infant.At present, the timing of screening and treatment of premature thyroid disease is still controversial.In this review, the thyroid function and outcome of premature infants under different pathological conditions are summarized and analyzed to provide a reliable basis for rational selection of screening opportunities and treatment strategies for thyroid diseases in clinical practice.

Objective:To systematically evaluate the effects of oral stimulation combined with non-nutritional sucking on premature infants feeding.Methods:From the establishment of the databases to December 14, 2020, PubMed, Embase, Cochrane Library and SinoMed, CNKI, Wanfang databases were searched for randomized controlled trials (RCT) on oral stimulation combined with non-nutritive sucking in preterm infants. The gestational age (GA) of the infants was 26~37 w.The control group received routine nursing or sham treatment and the intervention group received oral stimulation and non-nutritional sucking on the basis of routine nursing. The intervention strategy included infant oral motor intervention and oral sensorimotor intervention. The literature were reviewed and the quality of RCTs evaluated. RevMan 5.3 software was used for meta-analysis.Results:A total of 20 RCTs were included, including 1 316 premature infants (GA 26~36 w). Compared with the control group, the intervention group had significantly shorter duration of hospital stay ( WMD=-3.45, 95% CI -4.41~-2.50, P<0.001). Significant differences existed in the corrected GA of discharge ( WMD=-0.68, 95% CI -1.10~-0.26, P=0.001), the age of total oral feeding(TOF) ( WMD=-5.22, 95% CI -9.04~-1.40, P=0.007), corrected GA of TOF ( WMD=-1.02, 95% CI -1.40~-0.64, P<0.001) and the body weight on TOF day ( WMD=-59.75, 95% CI -114.55~-4.95, P=0.030). Conclusions:Oral stimulation combined with non-nutritive sucking can accelerate TOF and shorten hospital stay in premature infants. The procedure should be standardized and promoted as routine and standard care for premature infants.

Clinical data of a child with acromesomelic dysplasia Maroteaux type (AMDM) treated in the Department of Pediatrics, Tianjin Medical University General Hospital at November 2018 was retrospectively analyzed.The female child aged 3 years and 3 months old with 83 cm height (-3.84 SD) had clinical manifestations of disproportionate short stature, disproportionate shortening of forearms and forelegs, and stubby fingers and toes.Gene sequencing identified compound heterozygous mutations, c.1640T>A(p.Val547Asp)/c.682G>A(p.Gly228Ser), in the NPR2 gene, which have not been reported in the Human Gene Mutation Database.Their protein function was predicted harmful.The child was diagnosed as AMDM.During the follow-up until 4 years and 8 months old, the child was 90 cm tall (-4.35 SD), with a growth velocity of 4.9 cm/year.She was treated with recombinant human growth hormone (rhGH) treatment for 9 months and regularly followed up.The child was now 98.2 cm height (-3.07 SD) and she had a growth velocity of 10.9 cm/year.This case report enriched the gene mutation spectrum of AMDM.Treatment with rhGH can effectively improve the height of the child, but the long-term effect needs further follow-up and observation.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

With the nationwide popularization of neonatal heel blood screening, and the change of screening standards and the improvement of premature infant survival rate, the incidence of congenital hypothyroidism in newborns has been increasing year by year.Some of these children need to take medication for all lifetime to maintain normal thyroid function, this is called persistent congenital hypothyroidism, while others don′t, is called transient congenital hypothyroidism.Causes of transient hypothyroidism include iodine deficiency, maternal thyrotrophin receptor blocker antibodies, maternal antithyroid medication, maternal or neonatal iodine exposure, premature delivery, and neonatal hepatic hemangioma.In this review, the author describes the etiology and management of children with transient hypothyroidism, meanwhile summarize several predictors of transient hypothyroidism.